To help elucidate the complex gene interactions thought to underlie the neural effects of alcohol, our research group has instituted a replicated bidirectional selective breeding program which has produced the HOT and COLD lines of mice, bred for differing sensitivity to the hypothermic effect of ethanol. Thermoregulation provides a useful and interesting system for investigating sensitivity to ethanol. Although it is clear that the serotonergic neurotransmitter system is involved in mediating differences in ethanol-induced hypothermia between the HOT and COLD selected lines, the mechanism (e.g., the specific receptor subtype involved) is less clear. Recent research implicates the serotonin 1B (5-HT1B) receptor in mediating several ethanol induced effects, including hypothermia. To specifically address the role of the serotonin 5-HT1B receptor in mediating ethanol-induced hypothermia, this proposal will study ethanol- induced hypothermia in HOT and COLD mice, as well as null mutants for the serotonin 5-HT1B receptor. These experiments will increase our understanding of genetic factors mediating ethanol's effects, and could help in developing pharmacotherapies for alcohol abuse.